Montelukast Inhibits Matrix Metalloproteinases Expression in Atherosclerotic Rabbits
- 10 December 2009
- journal article
- research article
- Published by Springer Science and Business Media LLC in Cardiovascular Drugs and Therapy
- Vol. 23 (6), 431-437
- https://doi.org/10.1007/s10557-009-6211-6
Abstract
Background Matrix metalloproteinases (MMPs) play important roles in the development and destabilization of atherosclerotic plaques. It is known that montelukast inhibits neointimal hyperplasia. However, the underlying mechanisms for the inhibitory effects of montelukast on neointimal formation have been poorly defined. Methods Thirty-six male New Zealand White rabbits were randomized as normal control, placebo (0.9% NaCl, 1.5 ml/kg/day, via intraperitoneal injection), atorvastatin (atorvastatin, 1.5 mg/kg/day, orally) and montelukast groups (montelukast, 1.5 mg/kg/day, via intraperitoneal injection). Atherosclerosis was induced by balloon-injury and high-cholesterol (HC) diet. Serum lipids were measured at 0, 8 and 12 weeks. After 12 weeks, the rabbits were sacrificed and histopathological changes examined. Immunohistochemistry and reverse transcription-polymerase chain reaction were used to measure the expression of MMP-2 and MMP-9 in the plaques. Results It was found that montelukast reduced neointimal formation, decreased macrophage accumulation, and increased smooth muscle cells. It also attenuated the expression of MMP-2 and MMP-9 in atherosclerotic plaques, but it had no effect on plasma lipid levels. Conclusion These data indicate that montelukast inhibits neointimal hyperplasia in association with decreased expression of MMP-2 and MMP-9 independent of plasma lipid levels in atherosclerotic plaques after vascular injury in hyperlipidemic rabbits.Keywords
This publication has 35 references indexed in Scilit:
- Anti-atherogenic effects of montelukast associated with reduced MCP-1 expression in a rabbit carotid balloon injury modelAtherosclerosis, 2009
- Leukotriene Signaling in Atherosclerosis and IschemiaCardiovascular Drugs and Therapy, 2008
- Multidrug Resistance Protein-1 Affects Oxidative Stress, Endothelial Dysfunction, and Atherogenesis via Leukotriene C 4 ExportCirculation, 2008
- Suppression of plasma matrix metalloproteinase-9 following montelukast treatment in childhood asthmaPediatrics International, 2007
- Prediction of atherosclerotic plaque ruptures with high-frequency ultrasound imaging and serum inflammatory markersAmerican Journal of Physiology-Heart and Circulatory Physiology, 2007
- Cysteinyl leukotrienes enhance tumour necrosis factor-?-induced matrix metalloproteinase-9 in human monocytes/macrophagesClinical & Experimental Allergy, 2007
- Montelukast protects against renal ischemia/reperfusion injury in ratsPharmacological Research, 2006
- Expression of 5-lipoxygenase and leukotriene A 4 hydrolase in human atherosclerotic lesions correlates with symptoms of plaque instabilityProceedings of the National Academy of Sciences of the United States of America, 2006
- Dual Role of Matrix Metalloproteinases (Matrixins) in Intimal Thickening and Atherosclerotic Plaque RupturePhysiological Reviews, 2005
- C-Type Natriuretic Peptide Inhibits Intimal Thickening of Rabbit Carotid Artery after Balloon Catheter InjuryBiochemical and Biophysical Research Communications, 1994